الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Inflammatory bowel disease either Crohn’s disease or ulcerative colitis are the main cause of IBD. Their etiology and pathogenesis remains unclear but it seems to be multifactorial. The main factors are genetic factors, environmental factors, and immunological factors.
Crohn’s disease can affect any segment of digestive tract with skip areas. The endoscopic features of Crohn’s disease are: in the early stage the mucosa is reddish purple showing aphthoid ulcers, in latter stages ulcerations are linear or serpiginous and the classic cobblestone appearance may arise, sinus tract, stricture, fistulas and fat wrapping. The microscopic features are sub mucosal lymphedema, lymphoid hyperplasia in lamina propria and sub mucosa, transmural involvement. The most important microscopic change seen in nearly 60% of patients is the presence of granulomas ”non caseating one”.
The ulcerative colitis disease affects only the colon with continuous symmetrical involvement. The endoscopic features include : the mucosa appears hyperemic ,edematous and granular in mild disease when the disease progresses the mucosa become heamorragic with visible punctuate ulcers and the patients may develop acute megacolon. The microscopic features include: edema of the lamina propria, congestion of the capillaries and this is followed by acute inflammatory cell infiltrate of neutrophils, lymphocytes, plasma cells, and macrophage.
Crohn’s disease and ulcerative colitis can be presentsd by chronic diarrhea, abdominal pain, weight loss, malnutrition, bleeding per rectum, anorexia, nausea, perianal symptoms or extra intestinal symptoms like anemia ,eye involvement, skin disorders like erythema nodosum and pyoderma gangrenosum and primary sclerosing cholangitis.
Diagnosis can be done by laboratory findings (complete blood count, CRP, and ESR), endoscopy, histopathology, radiology (CT enterocolonography, MRI enterocolonography).
The primary goal of medical therapy for IBD is directed toward the relief clinical symptoms. For both Crohn’s disease and ulcerative, medical therapy is generally considered as a two-step approach (1)achieving remission from symptoms of active disease ,and (2) maintaining remission .
To a large extent, the clinical presentation dictates the choice of pharmaceutical agent. Patients with sever disease generally require more aggressive therapy, whereas patients with milder disease may do well with less potent medications or no therapy at all. All medical therapeutic options carry risks of toxicity, and this risk must be considered carefully against the potential benefit.
Thiopurines are drugs were used in treatment of Crohn’s disease and ulcerative colitis (azathioprine and 6-mercaptopurine) they are purine analogs that function as immunosuppressive agents.
Azathioprine is converted to 6-MP nonenzymatically. 6-MP is then converted via three distinct metabolic pathways to various metabolites, including the therapeutic metabolites, 6-thioguanine nucleotides. Both medications have been demonstrated to be effective for achieving and maintaining remission in Crohn’s disease. Moreover, they can help to heal fistulae and minimize steroid use. They are typically reserved for use in patients with moderate to sever disease due to their increased toxicity profile, which includes hepatitis, nausea, and pancreatitis. Perhaps the most serious common side effect is leukopenia, which can be life threatening. Several studies have suggested an increased risk of lymphoma, although the absolute risk appears to be well below 1%.
Standard therapeutic dosage of azathioprine is 2-2.5mg/kg/day and the therapeutic dosage of 6-MP is 1-1.5mg/kg/day. Over the past several years, studies have shown that 80%of patients willhave an appropriate response to azathioprine/6-mercaptopurine (AZA/6-MP) if a serum level of the active metabolite (6-thioguanine, 6TGN) of the drug achieves a therapeutic range (235-450pg/ml).
Therefore, dosage adjustment is no longer based solely on weight. Because another metabolite of AZA/6-MP, 6-methylmercaptopurine (6-MMP), is associated with abnormal liver tests, it has become routine to check the metabolite levels of AZA-6-MP after 3-4 weeks to be sure the dose is appropriate in regard to therapeutic level as well as risk for liver disease.
A minority of patients carry one or more mutant alleles in one of the genes that regulate thiopurine metabolism-thiopurine methyltransferase (TPMT). Patients carrying this mutation are highly susceptible to leucopenia, even with lower doses of drug. Therefore, it is common practice to test for this mutation prior to starting therapy with these medications.Patients homozygous for TPMT mutations (1%) should not be treated with azathioprine.